Over the past 30 years there has been a dramatic increase in the number of harmful algal blooms (HAB's) in coastal waters throughout the world. As a result, there are more toxic algal species, more algal toxins and more geographic areas impacted than ever before. When these toxic species proliferate, they may cause massive kills of fish and shellfish, wildlife mortality, human illness and death. One of these marine organisms, pseudo-nitzchia produces a neurotoxin, Domoic Acid (DA). Most of what we know about the human health effects of Domoic Acid has been derived from a single documented outbreak in Montreal Canada in 1987. Persons who ate mussels with high levels of DA suffered serious medical illnesses, including seizures and coma, and 3 people died. Survivors were left with a profound memory disorder, Amnesic Shellfish poisoning (ASP). Based upon animal models, regulatory levels of DA in shellfish were established. Within the past 17 years, DA levels have been close to or exceeded these safety levels at razor clam harvesting beaches on Native American Reservations in the Pacific NW. Recent data indicate that this population is currently at risk for significant, but preventable, neurobehavioral impairment (ASP) from razor clam consumption, with memory problems ranging from the low average to amnesic range. There appears to be a dose- response relationship between exposure and memory problems and the base rate of persons meeting the criteria for severe memory impairment, or ASP is 4.3%. The purpose of this 5 year longitudinal cohort study is to extend these findings to establish their clinical and public health significance. A prospective longitudinal cohort design of 735 Native Americans (ages 6 months to 75 yrs) from three Tribes, with nested case-control study of identified cases of "ASP" will be implemented. The health impacts of chronic, low level exposures to DA over time will be determined as well as the exposure and host factors associated with DA neurotoxicity. A new model of ASP, to include the potential for delayed or latent toxicity, recovery, and recurrence will be tested with state-of-the-art procedures for assessing human exposure (mobile technology) and behavioral neurotoxicity in infants, children, adults and geriatric groups. Findings will have a significant clinical and public health impact. The diagnosis and prognosis for ASP will be defined and established safety levels for exposure will be re-evaluated to insure they are protective of persons with long term, repeated exposure to DA. PUBLIC HEALTH RELEVANCE: This study investigates the health impacts of Amnesic Shellfish Poisoning, a new environmental health problem caused by repeated exposure to the marine biotoxin, Domoic Acid. The clinical syndrome and risk factors for human illness in a group of NW Coastal Native Americans will be identified.